Delivery of nucleic acid therapies to specific disease tissue and cells in the body is challenging due to large molecular weight, negative charge, and relatively poor stability especially in biological fluids that are rich in degrading enzymes (such as DNAse and RNAse). Many technologies for nucleic acid delivery utilize cationic lipids and polymers that form electrostatic complexes (such as lipoplexes and polyplexes) with negatively-charged nucleic acid constructs. These cationic systems can be inefficient for gene therapy (with plasmid DNA) or RNA interference therapy (with siRNA) due to lack of intracellular release and stability. In addition, cationic lipids and polymers can be toxic to cells and tissues.
Drug resistance is a primary hindrance for the efficiency of chemotherapy against osteosarcoma. Although chemotherapy has improved the prognosis of osteosarcoma patients after introduction of neo-adjuvant therapy in the early 1980's, the outcome has since plateaued at approximately 70% for 5 year survival. The remaining 30% of the patients eventually develop resistance to multiple types of chemotherapy. There thus remains a need to overcome both the dose-limiting side effects of conventional chemotherapeutic agents and the therapeutic failure incurred from multidrug-resistant (MDR) tumor cells.